1. Field of the Invention
This invention pertains to a composition comprising an effective amount of a publically available bacterial strain, Lactobacillus casei strain DN 114-001 as an aid to resisting rotavirus infection and diarrhea associated therewith, as well as reducing the severity and persistence of rotavirus diarrhea, in children up to 24 months of age. The invention also pertains to a method of supplementing the nutrition of infants up to 24 months of age with a fermented milk product fermented by L. casei DN 114-001 on a daily basis, as a diarrhea preventive, and in an effort to reduce frequency, severity and duration of diarrheal episodes. Importantly, L. casei DN 114-001 is effective, alone, as the sole bacterial agent in addressing diarrhea in infants up to 24 months of age.
2. Background of the Prior Art
Group A rotavirus is the leading cause of diarrhea among children aged 6 to 24 months worldwide. Rotavirus associated diarrhea causes 870,000 deaths/year principally in developing countries (1). Symptoms are watery diarrhea, frequently associated with severe dehydration (2) and malabsorption of nutrients (3, 4). Limited investigations by mucosal biopsy of infected infants have shown that rotavirus principally infects the cells of the small intestine. Introduction of fermented milk products in infant diet has been proposed for the prevention or treatment of acute diarrhea (4, 5-10). These products contribute to a well balanced diet and contain lactic acid bacteria (LAB) which are known for their healthful influence, especially in infants (11). Clinical and experimental studies have reported preventive and protective effects of LAB consumption on rotavirus diarrhea. Incidence of diarrhea and rotavirus shedding have been reduced in infants receiving the bacterial association Streptococcus thermophilus and Bifidobacterium bifidum (12). After oral rehydration, a significant reduction of diarrheal symptoms have been observed when infants consumed Lactobacillus casei strain GG (13-15), Lactobacillus reuteri (15) or a milk fermented by Bifidobacterium longum (16). The mechanisms involved in this protection remain poorly understood.
In a previous study, we have developed a germ-free suckling rat model to study group A rotavirus associated diarrhea (17). In this model, 5-day old infected rats developed a 6-day diarrhea characterized by watery feces containing rotavirus antigens. Histological analyses have demonstrates that rotavirus infects enterocytes and induces cellular vacuolation in the small intestine. Clinical and histopathological analyses were assessed in infected suckling rats supplemented by a milk fermented by the Lactobacillus casei strain DN 114-001, which has been previously involved in a beneficial effect on diarrhea in children (18).
Infants of age up to 24 months experience a transitioning diet, which typically proceeds from mother""s milk or a formula substitute therefore, to soft and semi-soft cereals, to a wide variety of liquid, soft and hard foods at the upper range of the age bracket addressed herein. Applicants"" invention resides in the discovery that a diet nutrient, comprising a bacterial agent wherein the bacterial agent consists of Lactobacillus casei strain DN 114-001 is an aid in preventing the occurrence of rotavirus infection-associated diarrhea, reducing its severity and reducing its duration. The nutrient supplement is preferably a fermented milk product containing viable L. casei strains in the amount of at least 106 CFU/g, preferably at least 108 CFU/g and most preferably at least 1010 CFU/g. Daily doses of 10-20 grams/kg body weight for a concentration of 108 CFU/g are demonstrated effective in the treatment of rotavirus associated diarrhea. Preferably, at this concentration, a daily dose of 10-15 g/kg is administered.
The L. casei strain DN 114-001 is a publically available bacterial strain and it may a be readily obtained from the CNCM, Institute Pasteur, 25 Rue du Docteur Roux, Paris, France, under accession number I-1518. This deposit is made pursuant to Budapest Treaty Conditions, and all reservations as to its availability have been irrevocably removed. DN 114-001 is also present in the product Actimel, together with other bacterial agents, in Europe.
The preparation of milk fermentation products is known, per se, and does not constitute an aspect of the invention. Any fermented milk product which does not otherwise aggravate digestion, or present digestion problems, fermented by L. casei DN 114-001 is acceptable.
It is to be noted that the invention resides in the recognition that L. casei DN 114-001 is, in and of itself, an effective bacterial agent for the treatment of rotavirus-associated diarrhea. While this agent may optionally be combined with other bacterial agents, such as the 4-strain agent of French Patent Publication 2,739,869 dated Apr. 18, 1997, Applicants are the first to identify this specific strain as effective alone in preventing diarrhea, and reducing its severity, in infants up to 24 months of age.